An inactivated hand-foot-and-mouth disease vaccine using the enterovirus 71 (C4a) strain isolated from a Korean patient induces a strong immunogenic response in mice

Abstract

Enterovirus 71 (EV71) is a major causative agent of hand-foot-and-mouth disease (HFMD) frequently occurring in children. HFMD induced by EV71 can cause serious health problems and has been reported worldwide, particularly in the Asia-Pacific region. In this study, we assessed the immunogenicity of a formalin-inactivated HFMD vaccine using an EV71 strain (FI-EV71 C4a) isolated from a Korean patient. The vaccine candidate was evaluated in mice to determine the vaccination doses and vaccine schedules. BALB/c mice were intramuscularly administered 5, 10, or 20 μg FI-EV71 vaccine, followed by a booster 2 weeks later. EV71-specific antibodies and neutralizing antibodies were induced and maintained until the end of the experimental period in all vaccinated groups. To determine the effectiveness of adjuvant for the EV71 vaccine, three adjuvants, i.e., aluminium hydroxide gel, monophosphoryl lipid A, and polyinosinic-polycytidylic acid, were administered separately with the FI-EV71 vaccine to mice via the intramuscular route. Mice administered the FI-EV71 vaccine formulated with all three adjuvants induced a significantly increased antibody response compared with that of the single adjuvant groups. The vaccinated group with triple adjuvants exhibited more rapid induction of EV71-specific and neutralizing antibodies than the other groups. These results suggested that the role of adjuvant in inactivated vaccine was important for eliciting effective immune responses against EV71. In conclusion, our results showed that FI-EV71 was a potential candidate vaccine for prevention of EV71 infection.

Seroprevalence of antibodies to enterovirus 71 and coxsackievirus A16 among people of various age groups in a northeast province of Thailand

“…EV71 vaccine strains used by 3 manufacturers in mainland China belong to subgenotype C4a, while that developed in Taiwan belongs to B4 and that in Singapore to B3 [ 46 ]. The results show that NT antibody induced by a C4a vaccine cross-neutralize EV71 subgenotypes B3, C2, C3, and C5 but not subgenotype A [ 47 ]; the NT antibody induced by a B4 vaccine strongly cross-neutralize B1, B5 and C4a, but poorly neutralize C4b [ 48 ]. The information above demonstrates that the relatedness between the vaccine strain and the circulating strain(s) should be considered for vaccine selection in each country.…”

Enhanced neutralizing antibody response induced by inactivated enterovirus 71 in cynomolgus monkeys

“…Inactivated vaccines are considered ideal owing to concerns with the potential for vaccine-derived virulent viruses, e.g., from poliovirus attenuated vaccine [ 24 – 26 ]. In particular, our group recently showed that formalin-inactivated HFMD vaccine using an EV71 strain was a potential candidate vaccine for prevention of EV71 infection [ 27 ]…”

Hand, foot and mouth disease in West Bengal, India: A preliminary report on clinicovirological trend over 3 successive years (2013–2015)

“…However, many vaccines including inactivated virus vaccines, attenuated live virus vaccines, subunit vaccines, DNA vaccines, and virus-like particle vaccines have been tried. [ 10 11 ] Inactivated virus vaccines are considered advantageous and promising. [ 12 13 ]…”